Human essential hypertension is characterized by increased total peripheral resistance resulting in high blood pressure. In normal individuals, vascular resistance is related to artery constriction brought about by contraction of smooth muscle cells in the artery wall. Thus in hypertension increased total peripheral resistance is associated with alterations in vascular smooth muscle cell contractile function. Most studies of vascular smooth muscle cell mechanics in hypertension have relied upon data obtained in whole artery preparations. However these data are complicated by the heterogeneous response of a large population of cells that are embedded in a dense connective tissue matrix. To avoid the complexities of multicellular preparations, smooth muscle mechanics will be studied directly, using state of the art techniques to measure mechanical responses from a single vascular smooth muscle cell. Single cells will be isolated from tail arteries of an animal model for human essential hypertension, the spontaneously hypertensive rat (SHR) and its normotensive control, Wistar Kyoto (WKY). Length:tension and force:velocity relationships will be obtained in single smooth muscle cells and correlated to the mechanics of the artery from which it was derived. Alterations in smooth muscle cell contractile properties will also be correlated to the content and profile of its contractile and cytoskeletal proteins. A possible pathogenic mechanism for hypertension is that in the development of the disease smooth muscle cells are subjected to mechanical strain resulting from elevated blood pressures. To test whether smooth muscle cells respond to strain by increasing their rate of contractile and cytoskeletal protein synthesis, cultured smooth muscle cells will be stretched on silicone rubber plates and protein synthetic rates determined. This proposal will be the first to correlate alterations in single vascular smooth muscle mechanics with changes in the cell's intracellular protein profile. In addition, the effect of stretch on smooth muscle cells will be investigated as a mechanism responsible for hypertension.